The long-term objective of this application is to increase our understanding of the role of opioid dependence in modifying the reinforcing effectiveness of opioid drugs. Although it is currently known that drug taking is initiated and can be maintained in the absence of dependence or withdrawal, the effect of dependence and withdrawal on the motivation to take drugs is not clearly established. More information on this topic may assist in the development of therapeutic drugs, and improved therapeutic intervention in the treatment of drug (particularly opioid) abuse. Rhesus monkeys are subjects in this evaluation and four different tasks are planned to evaluate this question. The ultra-short acting mu opioid receptor agonist, remifentanil, will be used to maintain behavior in each task. 1) Demand curves will be obtained by providing remifentanil as a consequence of increasing fixed ratio values in each daily session. 2) The conditioned reinforcing effects of remifentanil will be evaluated using an observing response task. 3) Animals will establish an indifference point between a standard dose of cocaine and a variable dose of remifentanil. 4) A delay discounting task will determine how much a standard dose of remifentanil is discounted when it is delayed. Once behavior is stable in each task, the animals will be given the opportunity to self-administer a single injection of 3.2 mg/kg morphine once daily on a chain FI 10'FR5 schedule. Dependence to this dose of morphine should develop over the course of 30 days, and changes in the ability of remifentanil to maintain responding 21 hours after each injection of morphine should be observed as well in each of the four tasks. The effect of omitting one or more injections of morphine will be determined on opioid-maintained responding. Finally, dependence intensity will be increased by providing morphine twice daily. Withdrawal-induced changes in behavior maintained by both remifentanil and morphine will be determined by substituting saline for one or two consecutive injections of morphine. Thus, the effects of different levels of morphine dependence, and different times of withdrawal will be determined on four different indices of the reinforcing effects of an opioid drug. An additional aim is to evaluate changes in brain blood flow using [15-O] H2O in PET scans with monkeys that are self-administering a mu opioid agonist. Blood flow changes during active vs passive drug administration will be compared, and this comparison evaluated visa vis similar extant data on cocaine in monkeys, as well as in humans.